Sample processing in immunohistochemical (IHC) applications, for example, and in other chemical and biological analyses may involve one or a number of various processing sequences or treatment protocols as part of an analysis of one or more samples. Typically, such treatment protocols are defined by organizations or individuals requesting analysis, such as pathologists or histologists working at a hospital, and may be further defined by the dictates of a particular analysis to be performed.
An in-situ hybridization (ISH) procedure, e.g. a fluorescence in-situ hybridisation (FISH) procedure, is traditionally a two day long manual procedure. Attempts have been made to automate parts of the procedure in order to shorten the processing procedure and to reduce the number of manual steps. For example, the first day pre-treatment procedure has been automated with an instrument VP2000™ (Vysis, Abbott Molecular), in which instrument a robot moves slides from one jar to another.
However, the problem so far has been to combine the pre-treatment steps of the first day and the washing steps of the second day with the strict physical and environ-mental requirements of the denaturation and hybridization steps in between. In these steps it is preferred to use small volumes of processing fluids and provide a precise control of the humidity in the processing chamber surrounding the processed tissue section, and to provide controlled heating and cooling in order to obtain consistent FISH results.
Automated IHC and ISH staining instruments have been introduced by Ventana Medical Systems Inc. (BenchMark™ and Discovery™) and VisionBiosystem (Bond™). A drawback with these instruments is that they only provide a fixed processing volume, i.e. the processing chamber is of a fixed volume. The processing chamber volume in the instrument is at least 100 micro liters.
The BenchMark™ instrument needs to cover the tissue section to be processed and the applied processing fluid with oil in order to reduce evaporation of the processing fluid. If not covered by oil, the evaporation of processing fluid will deteriorate the processing result.
The Bond™ instrument has a small processing chamber which is manually clamped over each tissue section and each carrier. By manually clamping the processing chamber over each carrier, an individual staining cavity is created.
In the PCT publication WO 2009/086048 A1, to Ventana Medical Systems Inc., capillary-gap-variance liquid application and removal is disclosed. One drawback to this system is that it requires a relatively complex mechanical apparatus including a motor for a each station and each station processes only one slide at a time.
In the PCT publication WO 2009/074154 A2, to Dako Denmark NS, an apparatus for processing a biological sample arranged on a first planar surface of a carrier is disclosed. The apparatus comprises a second planar surface arranged substantially parallel to said first planar surface and at a first distance from said first planar surface, said first planar surface and said second planar surface are arranged at an angle greater than zero degrees from the horizontal plane; supply means for supplying an amount of a liquid that is to be applied to said biological sample. The first planar surface and said second planar surface are configured to be arranged at a second distance from each other, said second distance being such that said supplied amount of liquid is distributed over said biological sample when said first planar surface and said second planar surface are brought to said second distance from each other.
The sample processing apparatus disclosed in 2009/074154 A2 is not configured to easily allow a rack of slides to be automatically inserted, processed and removed.
U.S. Pat. No. 6,623,701 B1, to Max-Planck Gesellschaft zur Forderung der Wissenschaften e.V., discloses a specimen chamber for the liquid treatment of at least one specimen. The chamber comprises a base plate and a carrier plate, between which a gap-formed accommodation space is formed for the specimen, whereby the base plate and carrier plate are held together with a clamping device in a frame arrangement, and in order to form the accommodation chamber they are separated from one another by spacer elements.
A drawback with the specimen chamber of U.S. Pat. No. 6,623,701 B1 is that each specimen chamber has to be manually assembled before the processing of a specimen can be started. To manually assembly the chamber requires several steps and the associated time and work for each step and requires some skills of the person assembling the chamber in order to get the parts of the chamber to be arranged in their correct position. This manual assembly process with many steps increases the opportunity for human errors.
The PCT publication WO 2006/116037, to Celerus Diagnostics Inc., discloses a sample processing system that may be configured to achieve rapid sample processing such as rapid histochemical processing. The processing system may involve a wave element that can use angular microscopic slide movements to cause repeated elimination and reapplication of a fluidic substance perhaps through the action of capillary motion in order to refresh a microenvironment adjacent to a sample such as a biopsy or other such sample. Through such refreshing of a microenvironment, depletion of the microenvironment is avoided and the time necessary for slide processing may be shortened.
Drawbacks with the sample processing system disclosed in WO 2006/116037 are that a confined fluidic environment around a sample on a slide is accomplished by using an opposing slide that in one end is hinged to one end of the slide carrying the sample causing. As with the other systems, multiple slides in a single rack cannot be automatically loaded and unloaded into the processing location. Further, this system utilizes a wicking mechanism in the form of a large cartridge of absorbable material, thus increasing the operational cost of the instrument.
Further, mixing of the fluid within the confined fluidic environment is accomplished by providing an angled movement of the opposing slide, i.e. by rotating the opposing slide around the hinge.
Some of the drawbacks with prior art instruments are that they require relatively large volumes, about 150-200 micro liters, of processing fluid, that they do not provide as good results as manual processing, that they do not automatically provide a processing chamber and that they do not provide a variable volume of processing fluid to be used by providing a processing chamber having a variable volume. Further many of the prior art instruments are relatively complex requiring a large number of moving parts. Further, the prior art instruments often require manual assembly or attachment of a cover or lid to form a capillary gap or they require an evaporation preventing liquid to be applied on a pool of processing reagent during incubation which typically results in a higher volume of reagent needing to be applied.
An aim of the present invention is to solve these and other problems and drawbacks with the prior art system. For example, an object of the present invention is overcome the drawback of having a complex mechanism that processes only one slide at a time.
Another object of the present invention is to overcome the drawbacks of horizontal carrier systems that require a vacuum to evacuate the capillary chamber.
Yet another object of the present invention is to solve the problem of having a fixed volume of processing fluid or of requiring a relatively large amount of processing fluid for automated protocols compared to the amount of fluid required for manual protocols of the same type.
Another object of the invention is to eliminate the problem of requiring separate complex mechanisms for mixing of a fluid on each single slide.